Peptide-Targeted Gold Nanoparticles for Photodynamic Therapy of Brain Cancer

Abstract

Targeted drug delivery using epidermal growth factor peptide-targeted gold nanoparticles (EGFpep-Au NPs) is investigated as a novel approach for delivery of photodynamic therapy (PDT) agents, specifically Pc 4, to cancer. In vitro studies of PDT show that EGFpep-Au NP-Pc 4 is twofold better at killing tumor cells than free Pc 4 after increasing localization in early endosomes. In vivo studies show that targeting with EGFpep-Au NP-Pc 4 improves accumulation of fluorescence of Pc 4 in subcutaneous tumors by greater than threefold compared with untargeted Au NPs. Targeted drug delivery and treatment success can be imaged via the intrinsic fluorescence of the PDT drug Pc 4. Using Pc 4 fluorescence, it is demonstrated in vivo that EGFpep-Au NP-Pc 4 impacts biodistribution of the NPs by decreasing the initial uptake by the reticuloendothelial system (RES) and by increasing the amount of Au NPs circulating in the blood 4 h after IV injection. Interestingly, in vivo PDT with EGFpep-Au NP-Pc 4 results in interrupted tumor growth when compared with EGFpep-Au NP control mice when selectively activated with light. These data demonstrate that EGFpep-Au NP-Pc 4 utilizes cancer-specific biomarkers to improve drug delivery and therapeutic efficacy over untargeted drug delivery.

Theranostic Agents for Photodynamic Therapy of Prostate Cancer by Targeting Prostate-Specific Membrane Antigen

“…S5B for the spectrum of the laser light). The 672-nm laser diode was chosen as it was previously used with success in prior studies (46) due to its proximity to the peak of Pc413 absorbance (676 nm) and because of the availability of laser diodes. Light was delivered through a GRIN-lens-terminate multimode fiber (OZ Optics) and tumors were illuminated with irradiance of 33.3 mW/cm 2 , radiant exposure of 150 J/cm 2 at 672 nm (Supplementary Methods).…”

“…The fluorescence was also observed in PC3flu tumors, but was 1.5-fold less than that in PC3pip tumors after 2 hours postinjection (P ¼ 0.029). High fluorescence was observed in the upper back of the animals at early time points, but was cleared after 24 hours postinjection; this is likely due to nonspecific accumulation in the fatty region of the neck (46). To confirm that binding of PSMA-1-Pc413 is specific to PSMA, in vivo competition experiments were performed.…”

Water soluble, multifunctional antibody-porphyrin gold nanoparticles for targeted photodynamic therapy

“…15 The use of PEG to provide water solubility to the nanoparticles has been applied by Burda and co-workers for the synthesis of gold nanoparticles containing a noncovalently bound silicon phthalocyanine. [16][17][18][19] PEG has also been used to provide water solubility and to enhance in vivo accumulation in the tumour tissue by the enhanced vascular permeability and retention effect of gold nanoparticles functionalised with a hydrophobic zinc phthalocyanine. 20 Furthermore, PEG can also be a key building block in the synthesis of nanosystems for targeted photodynamic therapy.…”

Peptide‐Based Supramolecular Nanodrugs as a New Generation of Therapeutic Toolboxes against Cancer

“…[82] Hong et al synthesized a cRGD peptidepyropheophorbide-a (Pyro) conjugate for PDT. [89] Barberi-Heyob et al fabricated multifunctional NPs by using neuropilin-1 (NRP-1) to conjugate silica and the MRI agent Gd for PDT and MRI. [84] The Asn-Gly-Arg (NGR) targeting sequence was used to conjugate platinum (Pt) anticancer drugs.…”